Table 1.
Genotypes and significant clinical features observed in patients with Type 2 Gaucher disease
| Alleles | Protein | cDNA | Age at diagnosis |
Age at death |
Hydrops | Ichthyosis | Hepatosplenomegaly | Seizures | Additional clinical information |
Reference |
|---|---|---|---|---|---|---|---|---|---|---|
| 55 bp del/Met416Val | p.Met455Val | c.1263del55/c.1363A>G | 8 months | 17 months | Yes | [12] | ||||
| 55bp del / Arg285His | p.Arg324His | c.1263del55/c.971G>A | At birth | Perinatal | Unknown | [13] | ||||
| 55bp del/Arg257Gln | p.Arg296Gln | c.1263del55/c.887G>A | At birth | 3 weeks | Yes | Yes | [13] | |||
| Ala190Glu/Gly325Arg | p.Ala229Glu p.Gly364Arg |
c.686C>A/c.1090G>A | 9 months | Unknown | Unknown | [13] | ||||
| Arg120Trp/Ser196Pro | p.Arg159Trp p.Ser235Pro |
c.475C>T/c.703T>C | At birth | 3 months | Yes | Yes | Yes | Laryngospasm | [70] | |
| Arg120Trp/Ser196Pro | p.Arg159Trp p.Ser235Pro |
c.475C>T/c.703T>C | At birth | 11 days | Yes | Yes | Yes (refractory) | [13] | ||
| Arg131Leu/Arg131Leu | p.Arg170Leu p.Arg170Leu |
c.509G>T/c.509G>T | 5 months | 7 months | Yes | Developmental regression | [13] | |||
| Arg131Leu/Arg131Leu | p.Arg170Leu p.Arg170Leu |
c.509G>T/c.509G>T | Prenatal | 9 months | Yes | Yes | [71] | |||
| Arg359X/Val398Phe | p.Arg398X p.Val437Phe |
c.1192C>T/c.1309G>T | At birth | 4 weeks | Yes | Facial dysmorphy (triangular face, malformed ears) | [72] | |||
| Arg463His/Arg463His | Arg502His Arg502His |
c.1505G>A/c.1505G>A | At birth | 1 month | Yes | Yes | Yes (myoclonic) | Respiratory failure | [73] | |
| Asp409His + His255Gln/Asp409His + His255Gln | Arg448His + His294Gln/Asp448His + His294Gln | c.[1342G>C; c.882T>G]/c.[1342G>C; c.882T>G] | 1 month | Unknown | Unknown | [74] | ||||
| Asp409His + His255Gln/Asp409His + His255Gln | Asp448His + His294Gln/Asp448His + His294Gln | c.[1342G>C; c.882T>G]/c.[1342G>C; c.882T>G] | 8 months | 2 years | Brainstem involvement; developmental regression | [74] | ||||
| c.533delC/c.533delC | c.533delC/c.533delC | Prenatal | 22 weeks gestation | Yes | Yes | External abnormalities (rocker bottom feet, flat nose) | [5,75] | |||
| c.84GG/Asp409His | Asp448His | c.84dupG/c.1342G>C | 5 months | Unknown | Abnormal eye saccades; delayed cognition | [74] | ||||
| Cys16Ser/Cys16Ser | Cys55Ser/Cys55Ser | c.164G>C c.164G>C |
Postmortem | At birth | Unknown | [76] | ||||
| Cys16Ser/Cys16Ser | Cys55Ser/Cys55Ser | c.164G>C c.164G>C |
Prenatal | 33 weeks gestation | 4th unsuccessful pregnancy for couple | [76] | ||||
| Gly202Arg/Gly202Arg | Gly241Arg/Gly241Arg | c.721G>A c.721G>A |
5 months | Unknown | Unknown | [13] | ||||
| Gly202Arg/Gly202Arg | Gly241Arg/Gly241Arg | c.721G>A c.721G>A |
6 months | Unknown | Unknown | [13] | ||||
| His311Arg/His311Arg | His350Arg/His350Arg | c.1049A>G c.1049A>G |
Prenatal | At birth | Yes | Yes | [72] | |||
| His311Arg/His311Arg | His350Arg/His350Arg | c.1049A>G c.1049A>G |
Prenatal | At birth | Yes | Yes | [72] | |||
| IVS2 + 1 G>A/Phe251Leu | Phe290Leu | c.115+1G>A/c.870C>A | 16 days | 1 month | Decreased spontaneous movement | [74] | ||||
| IVS2 + 1 G>A/Phe251Leu | Phe290Leu | c.115+1G>A/c.870C>A | At birth | 1 month | Yes | Yes | Myoclonic jerks/tremors | [77] | ||
| IVS2 + 1 G>A/RecNciI | c.115+1G>A/* | Prenatal | 45 days | Yes | Yes | Yes | [78] | |||
| IVS2 + 1 G>A/RecNciI | c.115+1G>A/* | Unknown | Unknown | Oculomotor apraxia; developmental regression | [74] | |||||
| Leu444Pro + Glu326Lys/Pro182Leu | Leu483Pro + Glu365Lys/Pro221Leu | c.[1448T>C; c.1093G>A]/c.662C>T | At birth | 25 days | Yes | Yes | [79] | |||
| Leu444Pro/Arg131Cys | Leu483Pro/Arg179Cys | c.1448T>C/c.508C>T | 8 months | 10.5 months | Yes | Strabismus | [80] | |||
| Leu444Pro/Arg257Gln | Leu483Pro/Arg296Gln | c.1448T>C/c.887G>A | Unknown | Unknown | Extensor posturing of trunk and neck; dysconjugate and crossed gaze | [74] | ||||
| Leu444Pro/Arg257Gln | Leu483Pro/Arg296Gln | c.1448T>C/c.887G>A | 9 months | 3 years | Yes (myoclonic) | [81] | ||||
| Leu444Pro/Arg257Gln | Leu483Pro/Arg296Gln | c.1448T>C/c.887G>A | 7 months | Unknown | Yes | Strabismus; bilateral hearing loss; failure to thrive | [77] | |||
| Leu444Pro/Asp380Asn | Leu483Pro/Asp419Asn | c.1448T>C/c.1255G>A | Unknown | Unknown | Unknown | [74] | ||||
| Leu444Pro/c.330delA | Leu483Pro | c.1448T>C/c.330delA | 3 months | Unknown | Unknown | [13] | ||||
| Leu444Pro/Gln414X | Leu483Pro/Gln453X | c.1448T>C/c.1357C>T | 9 months | 10 months | Apneic spells; developmental regression; ophthalmoplegia | [74] | ||||
| Leu444Pro/Gln414X | Leu483Pro/Gln453X | c.1448T>C/c.1357C>T | 2 months | 10 months | Unknown | [74] | ||||
| Leu444Pro/Gly202Arg | Leu483Pro/Gly241Arg | c.1448T>C/c.721G>A | 8 months | 2.5 years | Yes (tonic) | [81] | ||||
| Leu444Pro/Ile260Thr | Leu483Pro/Ile299Thr | c.1448T>C/c.896T>C | 6 months | 21 months | Strabismus; facial dysmorphy; respiratory difficulties | [79] | ||||
| Leu444Pro/IVS2 + 1 G>T | Leu483Pro | c.1448T>C/c.115+1G>T | 6 months | 9 months | Brainstem involvement; developmental regression | [74] | ||||
| Leu444Pro/IVS 2+1G>A | Leu483Pro | c.1448T>C/c.115+1G>A | 4 months | Unknown | Unknown | [13] | ||||
| Leu444Pro/IVS 2+1G>A | Leu483Pro | c.1448T>C/c.115+1G>A | 4 months | Unknown | Unknown | [13] | ||||
| Leu444Pro/IVS2 + 1G>A | Leu483Pro | c.1448T>C/c.115+1G>A | 6.5 months | 1 year | Strabismus; hypotonia; swallowing difficulties | [82] | ||||
| Leu444Pro/IVS2 + 1G>A | Leu483Pro | c.1448T>C/c.115+1G>A | At birth | 9 months | Yes | Progressive difficulty swallowing; bilateral brain stem dysfunction | [82] | |||
| Leu444Pro/IVS2 + 1 G>T | Leu483Pro | c.1448T>C/c.115+1G>T | Unknown | 8.5 months | Apnea; hypotonia; hyperflexia; esotropia | [74] | ||||
| Leu444Pro/Leu385Pro | Leu483Pro/Leu424Pro | c.1448T>C/c.1271T>C | 11 months | 18 months | Yes | Ophthalmoplegia | [12] | |||
| Leu444Pro/Leu444Pro + Ala456Pro | Leu483Pro/Leu483Pro + Ala495Pro | c.1448T>C/c.[1448T>C; c.1453G>C] | 7 months | 10 months | Yes | Strabismus | [82] | |||
| Leu444Pro/Phe213Ile | Leu483Pro/Phe252Ile | c.1448T>C/c.754T>A | 1 year | 28 months | Ophthalmoplegia | [12] | ||||
| Leu444Pro/Phe213Ile | Leu483Pro/Phe252Ile | c.1448T>C/c.754T>A | 11 months | Unknown | Bone involvement; ophthalmoplegia | [12] | ||||
| Leu444Pro/RecNciI | Leu483Pro | c.1448T>C* | 5 months | 1 year | Yes | Strabismus; facial paralysis; poor gag | [8] | |||
| Leu444Pro/RecNciI | Leu483Pro | c.1448T>C* | 1 year | 22 months | Abnormal tone | [12] | ||||
| Leu444Pro/RecNciI | Leu483Pro | c.1448T>C* | 8 months | 18 months | Yes | Ophthalmoplegia | [12] | |||
| Leu444Pro/RecNciI | Leu483Pro | c.1448T>C* | 1 month | 6 months | Unknown | [74] | ||||
| Leu444Pro/Thr323Ile | Leu483Pro/Thr362Ile | c.1448T>C/c.1085C>T | 6 months | Unknown | Hand tremors | Strabismus; brainstem involvement; clonus in feet | [74] | |||
| Leu444Pro/Tyr304Cys | Leu483Pro/Tyr343Cys | c.1448T>C/c.1028A>G | 1 year | Unknown | Unknown | [13] | ||||
| Leu444Pro/Tyr304Cys | Leu483Pro/Tyr343Cys | c.1448T>C/c.1028A>G | 1 year | 2 years | Yes (myoclonic) | [81] | ||||
| Leu444Pro/Tyr304Cys | Leu483Pro/Tyr343Cys | c.1448T>C/c.1028A>G | 1 year | Unknown | Unknown | [74] | ||||
| Leu444Pro/Tyr313His | Leu483Pro/Tyr352His | c.1448T>C/c.1054T>C | 7 months | 10 months | Oculomotor apraxia; developmental regression | [74] | ||||
| Leu444Pro/Unknown | Leu483Pro | c.1448T>C | 7 months | 11 months | Yes | Yes | Strabismus | [8] | ||
| Leu444Pro/Unknown | Leu483Pro | c.1448T>C | Unknown | Unknown | Unknown | [74] | ||||
| Leu444Pro/Unknown | Leu483Pro | c.1448T>C | 8 months | 2.5 years | Yes | Yes | Absent gag | [8] | ||
| Lys198Glu/Lys198Glu | Lys237Glu/Lys237Glu | c.709A>G/c.709A>G | 16 months | 2 years | Yes | Yes (myoclonic) | [81] | |||
| Lys198Glu/Lys198Glu | Lys237Glu/Lys237Glu | c.709A>G/c.709A>G | Unknown | Unknown | Myoclonic jerks | Hypotonia; gaze abnormalities | [74] | |||
| Phe213Ile/Asn382Lys | Phe252Ile/Asn421Lys | c.754T>A/c.1263C>A | 10 months | 18 months | Unknown | [12] | ||||
| Phe213Ile/Leu383Arg | Phe252Ile/Leu422Arg | c.754T>A/c.1265T>G | 7 months | 26 months | Yes | [12] | ||||
| Phe213Ile/Lys74X | Phe252Ile/Lys113X | c.754T>A/c.337A>T | Unknown | 10 months | Yes (myoclonic) | Strabismus; ophthalmoplegia; apneic spells | [74] | |||
| Phe259Leu/Asn188Lys | Phe298Leu/Asn227Lys | c.894C>A/c.681T>G | At birth | Perinatal | Opisthotonus | [13] | ||||
| Pro122Leu/Val375Leu | Pro161Leu/Val414Leu | c.482C>T/c.1240G>C | 1 year | Unknown | Yes | [12] | ||||
| RecA/IVS 10 + 2 | *c.1505+2T>G | Prenatal | Prenatal | Yes | Yes | Ascites; pleural effusions | [74] | |||
| RecA/IVS 10+2 T>G | c.1505+2T>G | Prenatal | Prenatal termination | Yes | [82] | |||||
| RecB/RecB | * | Prenatal | 1 day | Yes | Yes | Yes | Facial dysmorphy | [8] | ||
| RecB/RecB | * | Prenatal | Miscarriage | Yes | Thymic hypoplasia | [8] | ||||
| RecD/RecD | * | Prenatal | Perinatal | Yes | [13] | |||||
| RecD/RecD | * | Prenatal | 2 hours | Yes | Yes | Yes | [83] | |||
| RecD/RecD | * | Prenatal | 1 hour | Yes | Yes | Yes | Hypokinesia; facial dysmorphy | [84] | ||
| RecG + Leu444Pro/Arg257Gln | Leu483Pro/Arg296Gln | *c.1448T>C/c.887G>A | 6 months | Unknown | Unknown | [13] | ||||
| RecNciI/Glu41Leu | Glu80Leu | *c.238G>A | Several months | 18 months | Yes | Failure to thrive | [80] | |||
| RecNciI/RecNciI | * | Prenatal | At birth | Yes | Yes | Hyperextension of neck | [71] | |||
| Ser196Pro/Ser196Pro | Ser235Pro/Ser235Pro | c.703T>C c.703T>C |
At birth | Perinatal | Respiratory difficulty | [13] | ||||
| Trp184Arg/Asp409His | Trp223Arg/Asp448His | c.667T>C c.1342G>C |
5 months | Unknown | Opisthotonos; hypertonia; increased gag reflex | [74] | ||||
| Tyr363Cys/Unknown | Tyr402Cys | c.1205A>G | 5 months | 15 months | Yes | [12] | ||||
| Unknown/Unknown | At birth | 2 months | Yes | Hyperextension of the neck; hypertonia; poor suck/swallow | [85] | |||||
| Unknown/Unknown | At birth | 1 week | Yes | Flat nose | [85] |
*
Rec D: recombination at the end of exon 7; Rec G: recombination in intron 10-exon 11 or the 3’ untranslated region; Rec A: Recombination in intron 3; Rec NciI: Recombinant allele in exon 10 containing L444P, A456P, and V460V